Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Vorinostat in Treating Patients With Locally Recurrent or Metastatic Cancer of the Urothelium

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI	CCC-PHII-61 6879, NCI-6879, NCT00363883

Objectives

Primary

1. Determine response rate (as measured by RECIST criteria) in patients with locally recurrent or metastatic transitional cell carcinoma of the urothelium treated with vorinostat (SAHA).

Secondary

1. Determine the time to progression and overall survival of patients treated with this regimen.
2. Determine the safety and toxicity profile of SAHA in these patients.
3. Determine, preliminarily, feasibility and clinical efficacy of SAHA using molecular correlates in tissue, oral mucosa, and blood.

Entry Criteria

Disease Characteristics:

• Pathological diagnosis of transitional cell carcinoma of the bladder or other sites of the urothelium
  • Less than 25% component of other cell types (e.g., small cell, neuroendocrine, or squamous cell carcinoma)
• Locally recurrent or metastatic disease
• Disease must have recurred or progressed on or subsequent to platinum-based chemotherapy in the adjuvant or advanced setting
• Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
  • Bone metastases allowed provided there is measurable nonosseous disease
• No known brain metastases
• Must be willing to undergo biopsy prior to study entry OR archival tumor tissue must be available for classification and correlates

Prior/Concurrent Therapy:

• See Disease Characteristics
• Prior second-line chemotherapy for this cancer allowed provided > 6 months elapsed from the completion of first-line chemotherapy to start of second-line chemotherapy
• Any number of prior intravesical therapies for superficial bladder cancer allowed
• One prior experimental biologic therapy for metastatic urothelial cancer allowed provided it was not an agent known to act through histone deacetylation or demethylation (e.g., sodium butyrate, trichostatin A, trapoxin, MS-27-275, or FR901228)
• More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• No more than 2 prior cytotoxic chemotherapy regimens for urothelial transitional cell cancer
• At least 2 weeks since prior valproic acid
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer agents or therapies

Patient Characteristics:

• Life expectancy > 3 months
• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 40 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No allergic reactions attributed to compounds of similar chemical or biological composition to vorinostat (SAHA), including any of the following:
  • Sodium butyrate
  • Trichostatin A (TSA)
  • Trapoxin (TPX)
  • MS-27-275
  • FR901228
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness or social situations that would limit study compliance

Expected Enrollment

A total of 37 patients will be accrued for this study.

Outcomes

Objective tumor response rate as measured by RECIST criteria

Time to progression
Overall survival
Toxicity profile as measured by NCI CTCAE v3.0 at the beginning of each treatment course
Feasibility and clinical efficacy of vorinostat (SAHA) using molecular correlates in tissue, oral mucosa, and blood

Outline

This is a multicenter study.

Patients receive oral vorinostat (SAHA) twice daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and buccal mucosa collection and tumor biopsies (if accessible) at baseline and periodically during study for correlative studies. Samples are examined by gene expression profiling and immunohistochemistry.

After completion of study treatment, patients are followed for up to 26 weeks.

Cheung EM, Quinn DI, Tsao-Wei DD, et al.: Phase II study of vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in patients with advanced transitional cell urothelial cancer (TCC) after platinum-based therapy--California Cancer Consortium/University of Pittsburgh NCI/CTEP-sponsored trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-16058.

Trial Contact Information

Trial Lead Organizations

California Cancer Consortium

David Quinn, MD, Protocol chair		Ph: 323-865-3956 Email: diquinn@hsc.usc.edu

Registry Information
Official Title		Phase II Study of Oral Suberoylanilide Hydroxamic Acid (SAHA) in Recurrent or Metastatic Transitional Cell Carcinoma of the Urethelium
Trial Start Date		2006-06-21
Trial Completion Date		2009-06-30 (estimated)
Registered in ClinicalTrials.gov		NCT00363883
Date Submitted to PDQ		2006-06-13
Information Last Verified		2008-10-24
NCI Grant/Contract Number		CM62209, CM17101

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